Week 3 Nutrition Disorders Associated with Bioenergetics Lecture

Question 1

All three macronutrients will converge to form what molecule that feeds into a major energy production pathway?

Answer 1

Acetyl-CoA

Question 2

what are the products of glycolysis

Answer 2

2 ATP (4 net - 2ATP in prep phase), 2 NADH, 2 pyruvate

Question 3

in order for the oxidative phosphorylation of glycolysis dervied NADH to occur where what must occur and how?

Answer 3

NADH must enter the mitochondria. this can occur via the malate-aspartate shuttle or the glycerol 3-phosphate shuttle

Question 4

how much ATP can be made from one molecule of glucose?

Answer 4

30-38 ATP

Question 5

in glycolysis ATP is produced by ….which does not require….

Answer 5

substrate level phosphorlyation which does not require Oxygen

Question 6

All amino acids can be broken down into what…

Answer 6

1 of 7 metabolites that can feed into the TCA cycle

Question 7

what are ketogenic AA?

Answer 7

amino acids that are used for the synthesis of ketone bodies, that cannot feed into gluconeogenesis (these structure produce acetly-CoA which cannot be converted back to pyruvate)

Question 8

what are glucogenic AA?

Answer 8

AA that have carbon skeletons that can be used for gluconeogenesis during starvation

Question 9

Arsenate does what?

Answer 9

decouples ATP synthesis by interfering with Glycerladehyde-3-phosphate dehydrogenase. G3PD puts arsenate on G-3-P instead of phosphate. This becomes a problem becasue 1,3-BPG is not created and therefore ATP in not produced when it is converted to 3-PG.

G3P–>1,3-BPG–>3-PG and ATP

Question 10

what does arsenite do?

Answer 10

inhibits pyruvate dehydrogenase. Pyruvate is not converted to acetyl-CoA

Question 11

What is lactic acidosis?

Answer 11

the symptom that results from an accumulation of lactate (lactic acid) due to the inability of Pyruvate to be converted to acetyl-CoA and enter the TCA cycle.

Question 12

what are some causes of lactic acidosis?

Answer 12

Anything that causes pyruvate to accumulate: exercise (anaerobic glycolysis in muscle), pyruvate dehydrogenase deficiency (arsenite poisoning), eleaveted NADH/NAD+ ratio (NAD+ is needed for Pyruvate dehydrogenase to work)

Question 13

what does pyruvate kinase do?

Answer 13

converts PEP to pyruvate and produces ATP

Question 14

Pyruvate kinase deficiency presents as what? what cell type is it seen in?

Answer 14

Chronic Hemolytic Deficiency. the isozyme of PK that is affected is in RBCs.

Question 15

pyruvate kinase deficiency causes what?

Answer 15

lack of ATP in RBCs interferes with Na/K ATPase and causes ion imbalance. the RBC acquire abnormal morphology and splenic hemolysis occurs.

Question 16

Pyruvate Kinase Deificiency also causes the accumulation of what? why is this bad?

Answer 16

2,3-BPG (upstream of the ‘dam”). 2,3-BPG allosterically inhibits hexokinase which further decreases glycolysis AND has allosteric effects on Hb favoring the T-state and causing anemia.

Question 17

how prevalent is pyruvate kinase deficiency

Answer 17

1:20,000 whites. second most common cause of Chronic hemolytic anemia next to G6PD deficiency

Question 18

where does the TCA cycle occur?

Answer 18

mitochondrial matrix

Question 19

where is pyruvate dehydrogenase located? what is its fucntion

Answer 19

mitochondria, converts Pyruvate to Acetyl-CoA

Question 20

what is the function of pyruvate carboxylase?

Answer 20

converts pyrvate to oxaloacetate with biotin as a cofactor

Question 21

what does a PC deficiency result in? 3

Answer 21

pyruvate buildup (lactic acidosis), hypoglycemia, decrease in myelin sheath and neurotransmitters

Question 22

oxaloacetate is an important precursor for what? 3

Answer 22

gluconeogenesis, production of myelin sheath and neurotransmitters

Question 23

what are some symptoms of PC deficiency?

Answer 23

lactic acidosis, failure to thrive, neurological dysfunction

Question 24

how common is PC deficiency?

Answer 24

rare, 1:250,000 live births

Question 25

how can PC deficiency be treated?

Answer 25

depends on mutation but can try glucose administration, biotin, citrate (get TCA cycle going), triheptanoin (can be used to make ketone bodies converted back to acetyl CoA)

Question 26

pyruvate dehydrogenase (PDH) deficiency results in what? 3

Answer 26

limited acetyl-CoA, ATP decrease, and pyruvate accumulation (Lactic acidosis)

Question 27

what is clinical heterogeneity?

Answer 27

same muation with different presentation

Question 28

PDH def is what type of inheritance?

Answer 28

X-linked, although it is clinically heterogenous and seen equally in males and females (random X-inactivation)

Question 29

why is dichloroacetate a treatment for PDH deficiency?

Answer 29

inhibits the kinase that deactivates the enzyme used in PDH complex (thus allows for acetly-coa production)

Question 30

what does cyanide poisoning do?

Answer 30

blocks cytochrome oxidase (complex IV) of ETC by binding iron

Question 31

what are the effects of cyanide poisoning?

Answer 31

massive lactic acidosis due to a switch to anaerobic glycolysis

Question 32

there are trace amounts of cyanide in nuts, how do we not die?

Answer 32

the enzyme rhodanase in liver detoxifies these

Question 33

What is oxphos disease caused by?

Answer 33

caused by mutation in DNA that codes for proteins associated with oxidative phosphorylation

Question 34

what is Myoclonic Epilepsy and Ragged-Red Fiber Disease?

Answer 34

mitochondrial disorder caused by point mutation in the mtDNA gene that encodes for tRNAlys

Question 35

how does MERRF manifest?

Answer 35

late onset, muscle twitching, clumps of diseased mitochondria appear in muscle fiber (stain red)

Question 36

what is Leber’s hereditary optic neuropathy

Answer 36

mitochondrial disorder that is caused by mutation in Complex I of ETC

Question 37

how does leber’s hereditary optic neuropathy present itself?

Answer 37

acute blindness cuased by degeneration of optic nerve

Question 38

what is idebenone? what does it treat

Answer 38

a compound that boosts electron transport chain by bypassing Complex I (treates leber’s hereditary optic neuropathy)

Question 39

which organs rely mostly on FA oxidation for energy?

Answer 39

heart, muscle, liver

Question 40

what is MCAD deficiency?

Answer 40

an impaired ability to break down medium chain FA (C6-C12)

Question 41

how does MCAD present itself?

Answer 41

hypoketonic hypoglycemia triggered by prolonged fasting or exercise

Question 42

how do you treat MCAD?

Answer 42

high carb diet, acvoidance of fasting

Question 43

what is CPT II used for?

Answer 43

transport of FA into mitochondria

Question 44

CPT II def presents as?

Answer 44

rhabdomylosis: muscle breakdown and release of myoglobin

Question 45

what casues jamaican vomiting syndrome?

Answer 45

eating unripe Akee fruit produces MCPA which inhibits FA oxidation

Question 46

what is role of porpionyl-CoA carboxylase

Answer 46

plays a role in carboxylatin 3C FA that cannot be broken down into acetyl-CoA otherwise. has a biotin cofactor

Question 47

what does propionyl-CoA carboxylase deficiency result in?

Answer 47

organic acidemia

Question 48

persoxisomes break down which FAs

Answer 48

VLCFA and branched FA

Question 49

what are the disorders associated with peroxisomal FA oxidation?

Answer 49

x-linked adrenoleukodystrophy (cant transport VLCFA), zellweger syndrome (no peroxisome produced), adult refsum disease (loss of alpha oxidation, branched FA accumulate)

Question 50

why is buildup of VLCFA and branched FA bad?

Answer 50

disrupts myelin sheaths, neurologic damage, loss of motor fucntion

Question 51

why is it difficult to treat x-linked adenoleukodystrophy

Answer 51

cant limit VLCFA because the body synthesizes them on its own